This proposal presents an approach to the study of the regulation of the humoral immune response at the level of individual helper T and B lymphocytes. It is hoped that a better understanding of the mechanisms which serve to regulate antibody responses can be gained through an investigation of the characteristics and interactions of the individual T and B lymphocytes which participate in antibody responses. Techniques will be employed which allow the isolation and antigenic stimulation of individual antigen specific helper T and nonimmune and immune B cells. Such techniques have been particularly successful in studying the regulation of B cell antibody responses as these methods allow one to independently access several aspects of the B cells' antibody response to antigen. These techniques will be employed to study: 1) The T cell dependence of the generation of secondary B cells, 2) The specificity and functional capabilities of individual helper T lymphocytes in collaboration with both immune and nonimmune B cells, 3) The role of the Major Histocompatibility Complex gene products in regulating antibody responses to the antigen DNP-GL phi 9, 4) The mechanisms which function to regulate antibody responses once initiated and 5) The secondary B cell repertoire to a series of Cytochrome c protein antigens.